Medicine and Health Sciences Commons^™

Delivery Of Hand Care To Patients With High Anxiety Burden, Caellagh D Catley, Sarah C Romans, Abby L Cheng, Ryan P Calfee

2020-Current year OA Pubs

PURPOSE: To determine whether patients presenting with Patient-Reported Outcome Measurement Information System (PROMIS) anxiety scores at >95th percentile of the US population undergo elective hand surgery at rates different from patients with less anxiety. Secondarily, we aimed to assess surgeon notation of these patients' emotional states and incidences of postoperative complications.

METHODS: This single-center retrospective cohort study analyzed data from new adult patients presenting for hand care between January 2019 and December 2020. Patients with initial PROMIS anxiety scores ≥70 were identified as the high anxiety burden (HAB) group. For each patient with HAB presenting with carpal tunnel syndrome, trigger …

Targeting The Glutamine-Arginine-Proline Metabolism Axis In Cancer, Di Wang, Jiang-Jie Duan, Yu-Feng Guo, Jun-Jie Chen, Tian-Qing Chen, Jun Wang, Shi-Cang Yu

Faculty, Staff and Student Publications

Metabolic abnormalities are an important feature of tumours. The glutamine-arginine-proline axis is an important node of cancer metabolism and plays a major role in amino acid metabolism. This axis also acts as a scaffold for the synthesis of other nonessential amino acids and essential metabolites. In this paper, we briefly review (1) the glutamine addiction exhibited by tumour cells with accelerated glutamine transport and metabolism; (2) the methods regulating extracellular glutamine entry, intracellular glutamine synthesis and the fate of intracellular glutamine; (3) the glutamine, proline and arginine metabolic pathways and their interaction; and (4) the research progress in tumour therapy …

Biological Validation Of Peak-Width Of Skeletonized Mean Diffusivity As A Vcid Biomarker: The Markvcid Consortium, Alison M Luckey, Saptaparni Ghosh, Chen-Pin Wang, Alexa Beiser, Rebecca Bernal, Zhiguang Li, Djass Mbangdadji, Elyas Fadaee, Haykel Snoussi, Angel Gabriel Velarde Dediós, Hector A Trevino, Monica Goss, Laura J Hillmer, Christopher E Bauer, Adam M Staffaroni, Lara Stables, Marilyn Albert, Jayandra J Himali, Thomas H Mosley, Lars Forsberg, Vilmundur Guðnason, Baljeet Singh, Herpreet Singh, Kristin Schwab, Joel H Kramer, Gary A Rosenberg, Karl G Helmer, Steven M Greenberg, Mohamad Habes, Danny J J Wang, Brian T Gold, Hanzhang Lu, Arvind Caprihan, Myriam Fornage, Lenore J Launer, Konstantinos Arfanakis, Sudha Seshadri, Charles Decarli, Pauline Maillard, Claudia L Satizabal

Faculty, Staff and Student Publications

BACKGROUND: Peak-width of skeletonized mean diffusivity (PSMD), a neuroimaging marker of cerebral small vessel disease (SVD), has shown excellent instrumental properties. Here, we extend our work to perform a biological validation of PSMD.

METHODS: We included 396 participants from the Biomarkers for Vascular Contributions to Cognitive Impairment and Dementia (MarkVCID-1) Consortium and three replication samples (Cohorts for Heart and Aging Research in Genomic Epidemiology = 6172, Rush University Medical Center = 287, University of California Davis Alzheimer's Disease Research Center = 567). PSMD was derived from diffusion tensor imaging using an automated algorithm. We related PSMD to a composite measure …

Nuclear Expression Of Dynamin 2 Is Associated With Tumor Aggressiveness In Bladder Cancer Patients: A Bioinformatics And Experimental Approach, Mahdieh Razmi, Leili Saeednejad Zanjani, Mandana Rahimi, Roya Sajed, Sadegh Safaei, Zahra Madjd, Roya Ghods

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: Dynamin 2 (DNM2) is aberrantly expressed in different malignancies and exerts a function in tumor progression.

AIMS: This study, for the first time, aimed to evaluate the clinical and prognostic value of DNM2 in the pathophysiology of bladder cancer using bioinformatics analysis and experimental evaluation.

METHODS AND RESULTS: We analyzed gene expression of DNM2 in bladder tumor by GEPIA2 and GENT2 platforms. Cluster subnetworks were recognized from the protein-protein interaction (PPI) network using the MCODE plugin to screen the key genes. Subsequently, the pathway enrichment analysis was evaluated. Then, the immunohistochemical examination was conducted on 209 paraffin-embedded bladder cancer …

Relative Uptake Of Tomato Carotenoids By In Vitro Intestinal And Prostate Cancer Cells, Nancy E Moran, Brianna Alexander, Shivi Garg, Nathan Marchant, Noor A Hason

Children’s Nutrition Research Center Staff Publications

Background: Consumption of tomatoes and tomato carotenoids is associated with a reduced risk of prostate cancer. Prostate tissue accumulates tomato carotenoids, including lycopene, β-carotene, and phytoene. Phytoene accumulation is relatively greater in the prostate than that of lycopene, but the metabolic determinants of tissue carotenoid profiles are poorly understood.

Objectives: The purpose of this study was to determine if differences in stability, cellular uptake, and clearance of phytoene compared with lycopene or β-carotene by prostate and intestinal cells may explain differences in observed tissue carotenoid profiles.

Methods: Gene and protein expression for carotenoid metabolism in prostate cell lines were analyzed …

Are Prediction Models Moving Closer To Clinical Application In The Diagnosis Of Type Of Diabetes In Youth?, Fida Bacha

Children’s Nutrition Research Center Staff Publications

No abstract provided.

Genetic Architecture Of Cerebrospinal Fluid And Brain Metabolite Levels And The Genetic Colocalization Of Metabolites With Human Traits, Ciyang Wang, Chengran Yang, Daniel Western, Muhammad Ali, Yueyao Wang, Chia-Ling Phuah, John Budde, Lihua Wang, Priyanka Gorijala, Jigyasha Timsina, Agustin Ruiz, Pau Pastor, Maria Victoria Fernandez, Dominantly Inherited Alzheimer Network (Dian), Alzheimer’S Disease Neuroimaging Initiative (Adni), Daniel J Panyard, Corinne D Engelman, Yuetiva Deming, Merce Boada, Amanda Cano, Pablo Garcia-Gonzalez, Neill R Graff-Radford, Hiroshi Mori, Jae-Hong Lee, Richard J Perrin, Laura Ibanez, Yun Ju Sung, Carlos Cruchaga

Faculty, Staff and Student Publications

Brain metabolism perturbation can contribute to traits and diseases. We conducted a genome-wide association study for cerebrospinal fluid (CSF) and brain metabolite levels, identifying 205 independent associations (47.3% new signals, containing 11 new loci) for 139 CSF metabolites, and 32 independent associations (43.8% new signals, containing 4 new loci) for 31 brain metabolites. Of these, 96.9% (CSF) and 71.4% (brain) of the new signals belonged to previously analyzed metabolites in blood or urine. We integrated the metabolite quantitative trait loci (MQTLs) with 23 neurological, psychiatric and common human traits and diseases through colocalization to identify metabolites and biological processes implicated …

Navigating Physical Activity Promotion And Policy In The Post-Covid-19-Pandemic Era, Justin Richards, Katja Siefken, Michael Pratt, Adrian Bauman, Juliana Mejía-Grueso, Catherine B Woods, Wanda Wendel-Vos, Erica Hinckson, Deborah Salvo, Pedro C Hallal, Andrea Ramírez Varela

Faculty, Staff and Student Publications

Background: There is limited evidence on the priorities and opportunities associated with promoting population physical activity (PA) participation for the post-COVID-19-pandemic future.

Purpose: This study assessed government-led PA promotion efforts before and during the COVID-19 pandemic, along with post-COVID-19-pandemic priorities and recommendations.

Methods: Two separate cross-sectional surveys conducted in 2023. Survey 1 was targeted at the Global Observatory for Physical Activity (GoPA!) Country Contacts. Survey 2 also included key international informants representing influential stakeholders in PA policy implementation.

Results: There were 68 respondents to Survey 1, collectively representing 61 countries. An additional 37 people, including representatives from 14 key international …

Continuous Vital Sign Monitoring On Surgical Wards: The Cosmos Pilot, Nikola Anusic, Alper Gulluoglu, Elyad Ekrami, Edward J Mascha, Shuyi Li, René Coffeng, Alparslan Turan, Amber Clemens, Christine Perez, John W Beard, Daniel I Sessler

Faculty, Staff and Student Publications

Study objectives: Alerts for vital sign abnormalities seek to identify meaningful patient instability while limiting alarm fatigue. Optimal vital sign alarm settings for postoperative patients remain unknown, as is whether alerts lead to effective clinical responses reducing vital sign disturbances. We conducted a 2-phase pilot study to identify thresholds and delays and test the hypothesis that alerts from continuous monitoring reduce the duration of vital sign abnormalities.

Design: Two-phase pilot.

Patients: 250 adults having major non-cardiac surgery.

Setting: Surgical wards.

Intervention: All patients had routine vital sign monitoring by nurses at 4-h intervals. We initially continuously recorded clinician-blinded saturation, heart …

Off-Protocol Radiation Therapy In Phase 3 Metastatic Solid Tumor Trials, Alexander D Sherry, Timothy A Lin, Zachary R Mccaw, Esther J Beck, Ramez Kouzy, Joseph Abi Jaoude, Adina H Passy, Avital M Miller, Gabrielle S Kupferman, Clifton David Fuller, Charles R Thomas, Eugene J Koay, Chad Tang, Pavlos Msaouel, Ethan B Ludmir

Faculty, Staff and Student Publications

Purpose: Increasing data suggest that radiation therapy, particularly ablative radiation therapy, alters the natural history of metastatic disease. For patients with metastatic disease enrolled in prospective trials testing systemic therapy, the use of off-protocol radiation therapy to improve clinical symptoms or extend the duration of study systemic therapy may influence study endpoints. We sought to evaluate how often off-protocol radiation therapy was permitted among systemic therapy phase 3 trials, how often off-protocol radiation therapy is used, and whether off-protocol radiation therapy correlated with study outcomes.

Methods and materials: Two-arm, superiority-design, phase 3 randomized trials testing systemic therapy were screened from …

Prediagnostic Amino Acid Metabolites And Risk Of Gout, Accounting For Serum Urate: Prospective Cohort Study And Mendelian Randomization, Natalie Mccormick, Amit D Joshi, Chio Yokose, Bing Yu, Adrienne Tin, Robert Terkeltaub, Tony R Merriman, Oana Zeleznik, A Heather Eliassen, Gary C Curhan, Hang-Korng Ea, Matthew Nayor, Laura M Raffield, Hyon K Choi

Faculty, Staff and Student Publications

Objective: Our objective was to prospectively investigate prediagnostic population-based metabolome for risk of hospitalized gout (ie, most accurate, severe, and costly cases), accounting for serum urate.

Methods: We conducted prediagnostic metabolome-wide analyses among 249,677 UK Biobank participants with nuclear magnetic resonance metabolomic profiling (N = 168 metabolites, including eight amino acids) from baseline blood samples (2006-2010) without a history of gout. We calculated multivariable hazard ratios (HRs) for hospitalized incident gout, before and after adjusting for serum urate levels; we included patients with nonhospitalized incident gout in a sensitivity analysis. Potential causal effects were evaluated with two-sample Mendelian randomization.

Results: …

Whole-Of-School Physical Activity Promotion: Findings From Elementary Schools In The United States, Derek W Craig, Christopher D Pfledderer, Natalia I Heredia, Kevin Lanza, Kempson Onadeko, Andjelka Pavlovic, Jizyah Injil, Laura F Defina, Timothy J Walker

Faculty, Staff and Student Publications

INTRODUCTION: Schools can support students' participation in physical activity by offering opportunities consistent with a Whole-of-School (WOS) approach; however, the extent to which physical activity opportunities are provided and how school-level characteristics associate with their use remains unclear. This study examined how elementary schools' use a WOS approach to promote physical activity, as well as associations between school-level characteristics and physical activity opportunities provided.

METHODS: Survey data was collected from 162 elementary schools participating in the NFL PLAY 60 FitnessGram Project during the 2022-2023 school year. A WOS index (ranging from 0 to 12) was created from responses by school …

Economic Disadvantage During Childhood, Obesity, And Diabetes Across Three Birth Cohorts Of Older Mexicans, Jesús-Daniel Zazueta-Borboa, Rafael Samper-Ternent, Rebeca Wong, Neil Mehta

Faculty, Staff and Student Publications

OBJECTIVES: Diabetes prevalence has increased markedly in Mexico. We examined the individual and joint contributions of economic disadvantage during childhood (EDDC) and elevated body weight on diabetes prevalence in 3 cohorts of Mexican adults.

METHODS: Data on those 60-69 years old from the 1930-1939, 1940-1949, and 1950-1959 birth cohorts in Waves 1 (2001), 3 (2012), and 5 (2018) of the Mexican Health and Aging Study were used. EDDC was defined as the absence of a toilet in the household before age 10. Body mass status was defined using self-reported perceived body image at age 50. Diabetes was based on respondent …

Prevalence, Diagnostic Features, And Medical Outcomes Of Females With Turner Syndrome With A Trisomy X Cell Line (45, X/47, Xxx): Results From The Insights Registry, Natalia Klamut, Samantha Bothwell, Alexandra E Carl, Vaneeta Bamba, Jennifer R Law, Wendy J Brickman, Karen O Klein, Roopa Kanakatti Shankar, Catherina T Pinnaro, Patricia Y Fechner, Siddharth K Prakash, Iris Gutmark-Little, Susan Howell, Nicole Tartaglia, Marybel Good, Kelly C Ranallo, Shanlee M Davis

Faculty, Staff and Student Publications

Turner syndrome (TS) is defined by partial or complete absence of a sex chromosome. Little is known about the phenotype of individuals with TS mosaic with trisomy X (45,X/47,XXX or 45,X/46,XX/47,XXX) (~3% of TS). We compared the diagnostic, perinatal, medical, and neurodevelopmental comorbidities of mosaic 45,X/47,XXX (n = 35, 9.4%) with nonmosaic 45,X (n = 142) and mosaic 45,X/46,XX (n = 66). Females with 45,X/47,XXX had fewer neonatal concerns and lower prevalence of several TS-related diagnoses compared with 45,X; however the prevalence of neurodevelopmental and psychiatric diagnoses were not different. Compared to females with 45,X/46,XX, the 45,X/47,XXX group was significantly …

Covid-19 Risk Assessment Among Vulnerable Small Business Owners In El Paso County, Texas, Sadie H Conway, Denise Vasquez, Kristina D Mena, Louis D Brown, Soyoung Kwon, Janelle Rios

Faculty, Staff and Student Publications

Background: Our objective was to deliver actionable, worksite-specific COVID-19 risk assessments and mitigation strategies tailored to vulnerable workers in one of the highest-risk areas in the US.

Methods: Four trained, bilingual (English/Spanish) community health workers (CHWs) recruited small businesses (ie, ≤20 employees) across various industries and executed novel on-site infectious disease risk assessment surveys of at least one employer and one employee.

Results: Of 102 participating businesses (95% Hispanic-owned), 96% were characterized as "high risk" or "very high risk" for disease transmission. All businesses reported implementing at least one practice to reduce disease transmission; however, almost half of businesses lacked …

Bivariate Genome-Wide Association Study Of Circulating Fibrinogen And C-Reactive Protein Levels, Julie Hahn, Gerard Temprano-Sagrera, Natalie R Hasbani, Symen Ligthart, Abbas Dehghan, Alisa S Wolberg, Nicholas L Smith, Maria Sabater-Lleal, Alanna C Morrison, Paul S De Vries

Faculty, Staff and Student Publications

Background: Fibrinogen and C-reactive protein (CRP) play an important role in inflammatory pathways and share multiple genetic loci reported in previously published genome-wide association studies (GWAS), highlighting their common genetic background. Leveraging the shared biology may identify further loci pleiotropically associated with both fibrinogen and CRP.

Objectives: To identify novel genetic variants that are pleiotropic and associated with both fibrinogen and CRP, by integrating both phenotypes in a bivariate GWAS by using a multitrait GWAS.

Methods: We performed a bivariate GWAS to identify further pleiotropic genetic loci, using summary statistics of previously published GWAS on fibrinogen (n = 120 246) …

The Association Between Care Integration And Care Quality, Micah B Aaron, Michaela Kerrissey, Zhanna Novikov, Maike V Tietschert, Adam Scherling, Hassina Bahadurzada, Russell S Phillips, Anna D Sinaiko, Sara J Singer

Faculty, Staff and Student Publications

Objective: The study aims to analyze the relationship between care integration and care quality, and to examine if the relationship varies by patient risk.

Data sources and study setting: The key independent variables used validated measures derived from a provider survey of functional (i.e., administrative and clinical systems) and social (i.e., patient integration, professional cooperation, professional coordination) integration. Survey responses represented data from a stratified sample of 59 practice sites from 17 health systems. Dependent variables included three quality measures constructed from patient-level Medicare data: colorectal cancer screening among patients at risk, patient-level 30-day readmission, and a practice-level Healthcare Effectiveness …

Identification Of Proteins Associated With Type 2 Diabetes Risk In Diverse Racial And Ethnic Populations, Shuai Liu, Jingjing Zhu, Hua Zhong, Chong Wu, Haoran Xue, Burcu F Darst, Xiuqing Guo, Peter Durda, Russell P Tracy, Yongmei Liu, W Craig Johnson, Kent D Taylor, Ani W Manichaikul, Mark O Goodarzi, Robert E Gerszten, Clary B Clish, Yii-Der Ida Chen, Heather Highland, Christopher A Haiman, Christopher R Gignoux, Leslie Lange, David V Conti, Laura M Raffield, Lynne Wilkens, Loïc Le Marchand, Kari E North, Kristin L Young, Ruth J Loos, Steve Buyske, Tara Matise, Ulrike Peters, Charles Kooperberg, Alexander P Reiner, Bing Yu, Eric Boerwinkle, Quan Sun, Mary R Rooney, Justin B Echouffo-Tcheugui, Martha L Daviglus, Qibin Qi, Nicholas Mancuso, Changwei Li, Youping Deng, Alisa Manning, James B Meigs, Stephen S Rich, Jerome I Rotter, Lang Wu

Faculty, Staff and Student Publications

Aims/hypothesis: Several studies have reported associations between specific proteins and type 2 diabetes risk in European populations. To better understand the role played by proteins in type 2 diabetes aetiology across diverse populations, we conducted a large proteome-wide association study using genetic instruments across four racial and ethnic groups: African; Asian; Hispanic/Latino; and European.

Methods: Genome and plasma proteome data from the Multi-Ethnic Study of Atherosclerosis (MESA) study involving 182 African, 69 Asian, 284 Hispanic/Latino and 409 European individuals residing in the USA were used to establish protein prediction models by using potentially associated cis- and trans-SNPs. The models were …

Association Of Common And Rare Variants With Alzheimer’S Disease In More Than 13,000 Diverse Individuals With Whole-Genome Sequencing From The Alzheimer’S Disease Sequencing Project, Wan-Ping Lee, Seung Hoan Choi, Margaret G Shea, Po-Liang Cheng, Beth A Dombroski, Achilleas N Pitsillides, Nancy L Heard-Costa, Hui Wang, Katia Bulekova, Amanda B Kuzma, Yuk Yee Leung, John J Farrell, Honghuang Lin, Brian W Kunkle, Adam Naj, Elizabeth E Blue, Frederick Nusetor, Dongyu Wang, Eric Boerwinkle, William S Bush, Xiaoling Zhang, Philip L De Jager, Josée Dupuis, Lindsay A Farrer, Myriam Fornage, Eden Martin, Margaret Pericak-Vance, Sudha Seshadri, Ellen M Wijsman, Li-San Wang, Alzheimer's Disease Sequencing Project;, Gerard D Schellenberg, Anita L Destefano, Jonathan L Haines, Gina M Peloso

Faculty, Staff and Student Publications

INTRODUCTION: Alzheimer's disease (AD) is a common disorder of the elderly that is both highly heritable and genetically heterogeneous.

METHODS: We investigated the association of AD with both common variants and aggregates of rare coding and non-coding variants in 13,371 individuals of diverse ancestry with whole genome sequencing (WGS) data.

RESULTS: Pooled-population analyses of all individuals identified genetic variants at apolipoprotein E (APOE) and BIN1 associated with AD (p < 5 × 10

DISCUSSION: We observed that complementary pooled-population and subgroup-specific analyses offered unique insights into the genetic architecture of AD.

HIGHLIGHTS: We determine the association of genetic variants with Alzheimer's disease (AD) using …

Healthcare Disparities, Screening, And Molecular Testing In The Changing Landscape Of Non-Small Cell Lung Cancer In The United States: A Review, Razelle Kurzrock, Aadel A Chaudhuri, David Feller-Kopman, Narjust Florez, Jed Gorden, Ignacio I Wistuba

Faculty, Staff and Student Publications

Inequitable access to care continues to hinder improvements in diagnosis and treatment of lung cancer. This review describes healthcare disparities in the changing landscape of non-small cell lung cancer (NSCLC) in the United States, focusing on racial, ethnic, sex-based, and socioeconomic trends. Furthermore, strategies to address disparities, overcome challenges, and improve patient outcomes are proposed. Barriers exist across lung cancer screening, diagnosis, and treatment regimens, varying by sex, age, race and ethnicity, geography, and socioeconomic status. Incidence and mortality rates of lung cancer are higher among Black men than White men, and incidences in young women are substantially greater than …

Artificial Intelligence Uncertainty Quantification In Radiotherapy Applications – A Scoping Review, Kareem A Wahid, Zaphanlene Y Kaffey, David P Farris, Laia Humbert-Vidan, Amy C Moreno, Mathis Rasmussen, Jintao Ren, Mohamed A Naser, Tucker J Netherton, Stine Korreman, Guha Balakrishnan, Clifton D Fuller, David Fuentes, Michael J Dohopolski

Faculty, Staff and Student Publications

Background/purpose: The use of artificial intelligence (AI) in radiotherapy (RT) is expanding rapidly. However, there exists a notable lack of clinician trust in AI models, underscoring the need for effective uncertainty quantification (UQ) methods. The purpose of this study was to scope existing literature related to UQ in RT, identify areas of improvement, and determine future directions.

Methods: We followed the PRISMA-ScR scoping review reporting guidelines. We utilized the population (human cancer patients), concept (utilization of AI UQ), context (radiotherapy applications) framework to structure our search and screening process. We conducted a systematic search spanning seven databases, supplemented by manual …

A Confounding Pediatric Spinal Cord Injury: Anterior, Central, Or Both?, Mara Martinez-Santori, Anthony Kennedy, Autumn Atkinson, Stuart Fraser, Simra Javaid

Faculty, Staff and Student Publications

Pediatric spinal cord injury (SCI) most commonly affects the cervical region. Central cord syndrome most often occurs in the lower cervical injury due to hyperextension injury, while anterior cord syndrome is primarily due to vascular infarction after hyperextension injury. An unusual case of a pediatric patient who physically presented with central cord syndrome but radiologically had evidence of anterior spinal artery syndrome is described.A two-year-old male presented after a fall from three feet with flaccid upper extremities and dysesthesias but maintained functional strength in bilateral lower extremities. Although his clinical presentation was that of central cord syndrome, he was found …

Endovascular Thrombectomy For Childhood Stroke (Save Childs Pro): An International, Multicentre, Prospective Registry Study, Peter B Sporns, Kartik Bhatia, Todd Abruzzo, Lisa Pabst, Stuart Fraser, Melissa G Chung, Warren Lo, Ahmed Othman, Sebastian Steinmetz, Ulf Jensen-Kondering, Stefan Schob, Daniel P O Kaiser, Wolfgang Marik, Christina Wendl, Ilka Kleffner, Hans Henkes, Hermann Kraehling, Thi Dan Linh Nguyen-Kim, René Chapot, Umut Yilmaz, Furene Wang, Muhammad Ubaid Hafeez, Flavio Requejo, Nicola Limbucci, Birgit Kauffmann, Markus Möhlenbruch, Omid Nikoubashman, Peter D Schellinger, Patricia Musolino, Ali Alawieh, Jenny Wilson, Dominik Grieb, Alexandra S Gersing, Thomas Liebig, Martin Olivieri, Jaroslava Paulasova Schwabova, Ales Tomek, Panagiotis Papanagiotou, Grégoire Boulouis, Olivier Naggara, Christine K Fox, Kirill Orlov, Alexandra Kuznetsova, Carmen Parra-Farinas, Prakash Muthusami, Robert W Regenhardt, Adam A Dmytriw, Tanja Burkard, Mesha Martinez, Daniel Brechbühl, Maja Steinlin, Lisa R Sun, Ameer E Hassan, André Kemmling, Sarah Lee, Heather J Fullerton, Jens Fiehler, Marios-Nikos Psychogios, Moritz Wildgruber

Faculty, Staff and Student Publications

Background: Emerging evidence suggests that endovascular thrombectomy is beneficial for treatment of childhood stroke, but the safety and effectiveness of endovascular thrombectomy has not been compared with best medical treatment. We aimed to prospectively analyse functional outcomes of endovascular thrombectomy versus best medical treatment in children with intracranial arterial occlusion stroke.

Methods: In this prospective registry study, 45 centres in 12 countries across Asia and Australia, Europe, North America, and South America reported functional outcomes for children aged between 28 days and 18 years presenting with arterial ischaemic stroke caused by a large-vessel or medium-vessel occlusion who received either endovascular …

Neonatal Outcomes In Term And Preterm Infants Following Adjunctive Azithromycin Antibiotic Prophylaxis For Non-Elective Cesarean Delivery, Jane K Martin, Sherri A Longo, Victoria R Jauk, Erin A S Clark, George R Saade, Kim A Boggess, Sean Esplin, Ronald J Wapner, Michelle Y Owens, Sean C Blackwell, William W Andrews, Jeff M Szychowski, Alan T Tita

Faculty, Staff and Student Publications

Objective: It is currently unknown whether adjunctive azithromycin prophylaxis at the time of non-elective cesarean has differential effects on neonatal outcomes in the context of prematurity. The objective of this study was to compare whether neonatal outcomes differ in term and preterm infants exposed to adjunctive azithromycin prophylaxis before non-elective cesarean delivery.

Study design: A planned secondary analysis of a multi-center randomized controlled trial that enrolled women with singleton pregnancies ≥24 weeks gestation undergoing non-elective cesarean delivery (during labor or ≥4 h after membrane rupture). Women received standard antibiotic prophylaxis and were randomized to either adjunctive azithromycin (500 mg) or …

Association Of Late Eating With Colorectal Adenomas: A Cross-Sectional Study, Darbaz Adnan, Edena R Khoshaba, Mostafa Abel-Reheem, Jonathan Q Trinh, Yin Cao, Faraz Bishehsari

Faculty, Staff and Student Publications

Purpose: Colorectal cancer (CRC) is linked to lifestyle exposures. However, changes in the CRC rates among younger populations remain poorly understood and suggest the existence of yet unidentified factor(s) that may contribute to colon carcinogenesis. Here, we investigated the potential role of time of eating in the risk of pre-cancerous colonic neoplasms (tubular adenoma: TA).

Methods: We enrolled 663 participants undergoing screening colonoscopies. Data on food timing, dietary intake, sleep/wake patterns, and chronotype were collected through structured questionnaires. Late eating was defined as the consumption of food or snack within a 3-hour window of sleep onset for at least four …

High Activity Of The New Myeloablative Regimen Of Gemcitabine/Clofarabine/Busulfan For Allogeneic Transplant For Aggressive Lymphomas, Jeremy Ramdial, Ruitao Lin, Peter F Thall, Benigno C Valdez, Chitra Hosing, Samer Srour, Uday Popat, Muzaffar Qazilbash, Amin Alousi, Melissa Barnett, Alison Gulbis, Terri Lynn Shigle, Elizabeth J Shpall, Borje S Andersson, Yago Nieto

Faculty, Staff and Student Publications

Refractory aggressive lymphomas can be treated with allo-SCT, pursuing a graft-vs-lymphoma effect. While reduced intensity conditioning is safe, tumors often progress rapidly, indicating the need for more active conditioning regimens. The preclinical synergy we saw between gemcitabine (Gem), clofarabine (Clo) and busulfan (Bu) against lymphoma cell lines led us to study Gem/Clo/Bu clinically. Eligibility: age 12-65, refractory aggressive B-NHL, T-NHL or Hodgkin, with a matched donor. Infusional Gem was dose-escalated on days (d) -6 and -4 (475-975 mg/m2/day), followed by Clo (40 mg/m2/day) and Bu (target AUC, 4000 μMol min/day) (d -6 to -3). CD20+ tumors received rituximab. GVHD prophylaxis …

Cutaneous T Cell Lymphoma Atlas Reveals Malignant Th2 Cells Supported By A B Cell-Rich Tumor Microenvironment, Ruoyan Li, Johanna Strobl, Elizabeth F M Poyner, Aya Balbaa, Fereshteh Torabi, Pavel V Mazin, Nana-Jane Chipampe, Emily Stephenson, Ciro Ramírez-Suástegi, Vijaya Baskar Mahalingam Shanmugiah, Louis Gardner, Bayanne Olabi, Rowen Coulthard, Rachel A Botting, Nina Zila, Elena Prigmore, Nusayhah H Gopee, Marta A Chroscik, Efpraxia Kritikaki, Justin Engelbert, Issac Goh, Hon Man Chan, Harriet F Johnson, Jasmine Ellis, Victoria Rowe, Win Tun, Gary Reynolds, Dexin Yang, April Rose Foster, Laure Gambardella, Elena Winheim, Chloe Admane, Benjamin Rumney, Lloyd Steele, Laura Jardine, Julia Nenonen, Keir Pickard, Jennifer Lumley, Philip Hampton, Simeng Hu, Fengjie Liu, Xiangjun Liu, David Horsfall, Daniela Basurto-Lozada, Louise Grimble, Chris M Bacon, Sophie C Weatherhead, Hanna Brauner, Yang Wang, Fan Bai, Nick J Reynolds, Judith E Allen, Constanze Jonak, Patrick M Brunner, Sarah A Teichmann, Muzlifah Haniffa

Faculty, Staff and Student Publications

Cutaneous T cell lymphoma (CTCL) is a potentially fatal clonal malignancy of T cells primarily affecting the skin. The most common form of CTCL, mycosis fungoides, can be difficult to diagnose, resulting in treatment delay. We performed single-cell and spatial transcriptomics analysis of skin from patients with mycosis fungoides-type CTCL and an integrated comparative analysis with human skin cell atlas datasets from healthy and inflamed skin. We revealed the co-optation of T helper 2 (TH2) cell-immune gene programs by malignant CTCL cells and modeling of the tumor microenvironment to support their survival. We identified MHC-II+ fibroblasts and dendritic cells that …

Anti-Programmed Death Ligand 1 Plus Targeted Therapy In Anaplastic Thyroid Carcinoma: A Nonrandomized Clinical Trial, Maria E Cabanillas, Ramona Dadu, Renata Ferrarotto, Maria Gule-Monroe, Suyu Liu, Bryan Fellman, Michelle D Williams, Mark Zafereo, Jennifer R Wang, Charles Lu, Matthew Ning, Brian A Mckinley, Scott E Woodman, Dzifa Duose, Gary B Gunn, Naifa L Busaidy, Rare Tumor Initiative Team

Faculty, Staff and Student Publications

Importance: Anaplastic thyroid carcinoma (ATC) is a rare and lethal cancer. Although progress has been made in recent years in patients with mutated BRAF tumors, those who respond initially eventually die of their disease; furthermore, there are no approved therapies for non-BRAF mutated tumors.

Objective: To determine whether treatment with matched-targeted therapy plus immune checkpoint inhibitors were associated with improved overall survival (OS).

Design, setting, and participants: A phase 2 trial at a single center, tertiary institution with parallel cohorts, assigning treatment with targeted therapy according to the tumor mutation status. Patients with mutated BRAF V600E tumors received vemurafenib/cobimetinib plus …

Improving The Clinical Meaning Of Surrogate Endpoints: An Empirical Assessment Of Clinical Progression In Phase Iii Oncology Trials, Alexander D Sherry, Timothy A Lin, Zachary R Mccaw, Esther J Beck, Ramez Kouzy, Joseph Abi Jaoude, Adina H Passy, Avital M Miller, Gabrielle S Kupferman, Clifton David Fuller, Charles R Thomas, Eugene J Koay, Chad Tang, Pavlos Msaouel, Ethan B Ludmir

Faculty, Staff and Student Publications

Disease progression in clinical trials is commonly defined by radiologic measures. However, clinical progression may be more meaningful to patients, may occur even when radiologic criteria for progression are not met, and often requires a change in therapy in clinical practice. The objective of this study was to determine the utilization of clinical progression criteria within progression-based trial endpoints among phase III trials testing systemic therapies for metastatic solid tumors. The primary manuscripts and protocols of phase III trials were reviewed for whether clinical events, such as refractory pain, tumor bleeding, or neurologic compromise, could constitute a progression event. Univariable …

Association Between Socioeconomic Disadvantage And Risks Of Early And Recurrent Admissions Among Patients With Newly Diagnosed Heart Failure, Radha Dhingra, Hanzhang Xu, Bradley G Hammill, Scott M Lynch, Jessica S West, Michael D Green, Eric D Peterson, Lesley H Curtis, Matthew E Dupre

Faculty, Staff and Student Publications

Background: Socioeconomic disadvantage is associated with greater risks of hospital readmission and mortality among patients with heart failure (HF). However, it is less clear whether socioeconomic disadvantage has an immediate and lasting impact on the risk of admissions after the diagnosis of HF.

Methods: We used electronic health record data of patients aged 65 years and older with newly diagnosed HF between January 2015 and July 2018 in the Duke University Health System, with up to 8 years of follow-up. We assessed the association between neighborhood-level disadvantage, measured by the area deprivation index (lower, moderate, or higher) and hospital admissions …